p53 基因敲除鼠母鼠的催产素抑制所导致的早期生活压力会增加第一代和第二代成年期肿瘤的发生。
The early-life stress induced by oxytocin inhibition in p53 knockout mouse dams increases adulthood tumorigenesis in first and second generations.
机构信息
Experimental Oncology Department, IRCCS-European Institute of Oncology, Milan, Italy.
University of Modena and Reggio Emilia, Modena, Italy.
出版信息
Cancer Rep (Hoboken). 2023 Jan;6(1):e1625. doi: 10.1002/cnr2.1625. Epub 2022 May 11.
BACKGROUND
Early-life stress due to poor parental care has been suggested to increase cancer risk, though, so far, no experimental evidence established a link between defective parental behavior and spontaneous tumorigenesis in progeny. Essential maternal behavior is regulated, in particular, by the oxytocin (OT) hormonal circuit, which in turn responds to stimuli from the offspring and impinges on the central nervous systems.
METHODS
By providing L-368,899 OT receptor (OTR) inhibitor to lactating mothers, we set up a model of defective maternal care in p53 knockout mice.
RESULTS
The progeny of these dams showed, later in life, higher cortisol levels, shortened life span and increased tumorigenic potential of bone marrow cells (BMC). Notably, these phenotypes were transmitted to the following generation.
CONCLUSIONS
Therefore, the inhibition of OT function in mothers is a novel paradigm of early-life stress that is inherited across generations and increases cancer risk in tumor-prone mice.
背景
由于父母照顾不周而导致的早期生活压力被认为会增加癌症风险，但迄今为止，还没有实验证据表明父母行为缺陷与后代自发性肿瘤发生之间存在联系。基本的母性行为，特别是由催产素（OT）激素回路调节，而 OT 回路反过来又对来自后代的刺激做出反应，并影响中枢神经系统。
方法
通过向哺乳期的母亲提供 L-368,899 催产素受体（OTR）抑制剂，我们建立了一种 p53 敲除小鼠母性行为缺陷的模型。
结果
这些母鼠的后代在以后的生活中表现出更高的皮质醇水平、寿命缩短和骨髓细胞（BMC）的肿瘤发生潜能增加。值得注意的是，这些表型会传递给下一代。
结论
因此，母亲的 OT 功能抑制是一种新的早期生活压力范例，它可以在代际之间遗传，并增加易患肿瘤的小鼠的癌症风险。
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